Chromatography columns and their operaiton

ABSTRACT

A method of operating chromatography column apparatus comprising a column tube ( 101 ) and first and second discrete end cell structures, associated with the respective ends of the column tube and positionable to close off the column tube and define therein a column space for retaining chromatography medium in use of the apparatus. The first end cell portion comprises a piston portion ( 106 ) fitting slidably in the column tube. The column tube and the second end cell structure are separated to provide an access spacing between them. The piston portion ( 106 ) of the first end cell structure is advanced through the column tube to expose it at the open second end of the column tube, for maintenance of the piston portion thus exposed. Corresponding chromatography apparatus is another aspect of the disclosure.

FIELD OF THE INVENTION

This invention has to do with chromatography apparatus and methods. Itis particularly concerned with systems and methods for gaining access tocomponents of the column e.g. for maintenance, notably the column endcell structures.

BACKGROUND OF THE INVENTION

The present discussion relates to apparatus and methods useful inindustrial-scale chromatography, e.g. large-scale preparativepurification of fine chemicals and pharmaceuticals, including biologicalproducts. It is not concerned with laboratory-scale apparatus.Conventionally an industrial-scale chromatography column has acylindrical axially-vertical column tube with top and bottom end cells,each of which provides a strong backing plate with a fluid inlet/outletand support for a layer of mesh, sinter or other fluid-permeableretaining material which lets process liquid flow into and out of thechromatography space while retaining the bed of particulatechromatography medium. To provide adjustability and control of bedheight and bed compression, at least the top end cell is usually made inthe form of a piston slidable in the column tube interior. The bottomend cell may also be a piston but more usually is a fixed plate boltedagainst a bottom end flange of the column tube. Typically this bottomplate acts as a support for the column as a whole, being itselfsupported on legs or some other stand arrangement leaving clearance foroutlet pipework projecting beneath the bottom end cell.

Various mechanisms are known for controlling the position of the pistonend cell. The structure supporting the piston must move into the columninterior behind the piston, and so must be smaller than the columndiameter. Usually metal spacer posts are fixed to the back of the endplate and extend up axially—to a distance corresponding roughly to thelength of adjustment anticipated—to a lifting ring which is connected inturn down to an external drive and support mechanism able to move theend cell piston, via the spacer posts, relative to the fixed mounting.For example a set of lifting rods may extend up axially outside thecolumn from the fixed mounting to the lifting ring. The lifting rodsinclude (or are connected to) an axial drive, usually a mechanicalthreaded drive which may be hand-operated, to move the lifting ring upand down and thereby control the position of the end cell piston in thecolumn. Because the piston is large, close-fitting and acts on a bed offluid or particulate medium which may be packed, it is crucial that therate of raising or lowering the piston be carefully equalised around thecolumn and this requires care and time.

In the prior art, U.S. Pat. No. 5,681,474 describes a chromatographycolumn in which the top end cell plunger is carried by three rodsconnected to hydraulic drive cylinders, operated from a central controlto preserve alignment of the top cell as it is forced down onto themedia bed, especially to achieve flow packing.

WO 00/00259 describes a column in which the top end cell can be fullyretracted from the column tube by means of a set of threaded rods drivenin rotation.

Columns marketed by Chromaflow in the mid 90's also featured hydraulicdrives to move and if necessary withdraw upper and lower end cellplungers relative to the column tube.

From time to time in certain kinds of columns and processes it may bedesirable or necessary to get access to the column interior for purposesother than filling or emptying particulate medium, especially sincecolumns are now available which can do the latter through valved ports.In particular, column maintenance may require access to the inner partsof the end cells e.g. to remove their permeable retaining layers (meshor sinter) and/or their seals, for cleaning, replacement or repair. Forsuch access, the end cell must be withdrawn and separated from thecolumn tube, either entirely or at least with enough clearance to carryout the operation in question, e.g. removal/insertion of a permeablelayer element or seal. Typically access to the lower permeable elementis by unbolting a lower column tube flange from the bottom end cellplate, and lifting the column tube up away from the plate sufficientlyto unfasten and remove the permeable element sideways. Access to thepermeable element of the top (piston) end cell is by lifting the pistonright out of the column tube using the mechanism provided, sufficientlyfar for the permeable element to be moved in or out sideways.

The column elements being heavy, these operations normally have to bedone with the aid of cranes, powered drives or by manual mechanisms withsubstantial mechanical advantage. For the same reason, alignmentstructures are used to keep the column and its end cells axially alignedas they are separated from each other as described. This avoidspotential serious damage to precision components. The alignment andlifting structures cause significant obstructions around the tube, andneed to be carefully laid out to provide sufficient clearance at somepart of the circumference for insertion/removal of the permeableretaining elements if this is to be an operational requirement.

By way of illustration, a system and method working in line with knownprinciples (see U.S. Pat. No. 6,736,974) are described with reference toFIGS. 1 to 5, in which

FIGS. 1 and 2 show first and second stages for access to a lower endcell mesh, and

FIGS. 3, 4 and 5 show first, second and third stages for gaining accessto the upper end cell mesh.

In each Figure, views (a) and (c) are axial sections at the linesindicated in the top view (b).

First, the basic elements of the apparatus are described with referenceto FIGS. 1 and 2. A chromatography column consists essentially of asteel column tube 1 mounted on a bottom base plate 5, supported on theground through a set of legs 51. The column tube has integral top andbottom flanges 11,12 projecting perpendicularly around its top andbottom edges. The base plate 5 consists of a lower support plate 52 witha flat upper surface and an inner contoured cell plate 53. The cellplate 53 has a contoured surface with an array of support projectionsand intervening conduits (not shown) on which a permeable element (lowerend mesh) lies and is held in place by an array of fasteners. Amultiport access valve 55 communicates with the space above the cellplate through a central orifice in the bottom plate 5 to enableunpacking of chromatography medium and collection of eluent inprocessing; this is all established technology. The bottom tube flange12 seats down around the edge of the base plate 5, compressingperipheral seals and clamping the edge of the mesh, and is secured thereby bolt or stud fasteners 57.

The top cell 6 likewise has a rigid flat backing plate 62 and an innercontoured cell plate 63 for supporting an end mesh (not shown), butunlike the bottom end cell is configured as a piston slidable inside thecolumn tube. It is supported from above through acircumferentially-distributed array of vertical (axial) spacer rods 66whose bottom ends are screwed rigidly into the cell's backing plate 62,while their top ends screwed up into the inner periphery of an annularadjuster flange 7. The adjuster flange 7, sometimes called a liftingring, is spaced coaxially above the top column tube flange 11 and hasthe same OD but a smaller ID, so that it overhangs the column interiorfor securement to the spacer rods 66 that hold the piston 6.

Fluid communication through the top end cell 6 is through anothercentral access valve 65, similar to that in the bottom plate 5. Amongother functions, these access valves enable particulate medium to bepacked into and unpacked from the bed space of the column as a slurry,without opening the column.

Three vertical guide rods 71 have their top ends fixedly threaded intothe adjuster flange 7 at spaced locations (see views (b)). Each of theseguide rods 71 descends with clearance through a set of aligned guideholes through the upper and lower column tube flanges 11,12 and theperiphery of the column base 5.

Hydraulic drive cylinders 8 are mounted vertically on the underside ofthe outer base plate 52, and their driven rods 81 extend up throughfurther sets of aligned holes in the base 5, upper and lower column tubeflanges 11,12 and adjuster flange 7. Each lifting rod 81 is threadednear its top and has a pair of locating nuts 82 to either side of theadjuster flange 7 for fixing the flange to the rod 81 at a selectedposition. In this example there are three drive cylinders 8.

Further connecting structure is provided by a set of three vertical tiebars 73. These are short threaded rods received in openings through theadjuster flange 7 and top column tube flange 11, with respective pairsof locking nuts 74,75 to fix the location of each of these engagements.

Operation of the drive cylinders 8 directly raises or lowers theadjuster flange 7, to a height determined by the location of the driverod locknuts 82. The top end cell piston 6, being rigidly connected tothe adjuster flange 7 through the spacer rods 66, is raised or loweredcorrespondingly. If the tie rods 73 are locked by their locating nuts74,75 to both the adjuster flange 7 and column tube flange 11, the driverods 81 will lift the column tube 1 as well provided that it has firstbeen released from the base 5 by releasing the studs 57.

The following description of maintenance steps can now be followed.

To remove or gain access to the lower mesh or seals, the hydrauliccylinders are fully retracted to set the piston 6 to its lowermostposition. The studs 57 holding the column tube 1 to the base 5 areremoved. The tie rods 73 are locked to the upper column tube flange 11.Refer to FIG. 2. The hydraulic cylinders are then extended raising theadjuster flange 7, column tube 1 and top cell 6 away from the base. Theguide rods 71 slide through their aligned holes in the base to keep thecomponents in line and protect the hydraulic lifts from lateral forces.In this condition the lower mesh can be detached from its mounting 53and removed through the clearance between column tube 1 and base 5. Notein views (b) that the guide rods 71 are circumferentially spaced morewidely to the right of the view, providing a larger opening there forpassage of the mesh assembly.

Next, the known mode of removal of the upper mesh is described withreference to FIGS. 3, 4 and 5. Essentially the top piston 6 has to belifted out above the column tube 1. To achieve this, the piston 6 israised by the drives 8 to maximum operating height in the column, thetie rods 73 then being at full reach (FIG. 3). The tie rods are thenlocked at the adjuster flange 7 and tube flange 11, so that the adjusterflange 7 is supported fixedly by the column tube 1 and tie rods 73. Thedrive rods 81 can then be released from the flange 7, fully retractedand re-fastened with a new location on the flange 7 giving extra reach:see FIG. 4. The tie rods 73 are then fully released, and full advance ofthe hydraulic drives lifts the piston end cell 6 clear above the columntube 1 as seen in FIG. 5. The upper mesh can then be removed through theresulting clearance, between the two right-hand guide rods 71 which asbefore maintain the alignment of the components, and which by lockingrelative to the base 5 and or tube 1 support the piston 6 in its raisedposition. Throughout this operation the tube 1 preferably remains boltedto the base 5.

The described procedure and apparatus provide access to the two endcells without requiring overhead lifting equipment. Industrial columnscan be very large and heavy; typically the column diameter is 500 mm ormore. The illustrated column has a 1400 mm diameter and would be verydifficult to manoeuvre without a powered lift.

The described apparatus and procedure have however the drawback thataccess to the upper mesh is difficult; it has to be removed at quite adistance above the ground. For such a large and delicate component thisis a significant issue.

We also note the system described in WO 03/076923, which gets access tothe top end cell piston by connecting the piston centrally to anoverhead yoke. Once the piston has been lifted to the top of the columntube, this yoke can be released at one side and swung up and over tobring the piston (inverted) down beside the column. This gives loweraccess in the final position, but the swinging over of the piston wouldbe a risky matter with a large column, so that this proposal is limitedto smaller columns.

SUMMARY OF THE INVENTION

Aspects of our new proposals are new apparatus and techniques forimproving access to the piston end cell in operations of this kind.

A first aspect of our proposals is a method of operating chromatographyapparatus, the apparatus comprising a column tube having first andsecond ends, and first and second discrete end structures associatedwith the respective ends and defining with the column tube a columnspace for retaining chromatography medium in use of the apparatus, atleast the first end structure comprising a piston portion fittingslidably in the column tube. In the method, the column tube is separatedfrom the first and second end structures to provide access to thosestructures, e.g. for inspection, cleaning, repair, replacement orexchange or the like of parts, such as seal(s) and permeable retainingmembers (conveniently referred to herein using “maintenance” as acollective term). The characteristic feature in our first proposal isthat access to the first end structure is provided by moving the pistonthereof forwardly through the column tube to expose it at the opensecond end of the column tube, which is separated from the second endstructure to give access.

Compared with existing methods, this has the radical advantage that theaccess positions for the first and second end structures can berelatively close to one another. In the preferred orientation, where thefirst end and second end are the top and bottom respectively, the firstend structure appears below the column, greatly reducing the potentialaccess height requirement. Separation of the second end structure fromthe column—necessary for access to the second end structure—is alsoinvolved in access to the first end structure, potentially simplifyingthe procedure e.g. compared with that described above with reference toFIGS. 1 to 5 in which the column tube had to be lowered onto the base toexpose the top piston, inevitably covering the bottom end cell. In thepresent procedure, both may be accessible at the same stage.

The second end structure (usually the bottom) may remain fixed. Thecolumn tube may then be released from the fixed second end structure andmoved away from it axially to a position spaced from it. Then the pistonof the second end structure is moved through the column towards thesecond end structure and emerges at the second column end, the tube andsecond end structure remaining fixed during this movement. This is mostobviously practical where the first end is at the top and the column isan upright column on a stand. However different types of movement may beappropriate, e.g. to hold the column tube and lower the second endstructure away from it.

Preferably a powered drive such as a hydraulic drive is used to spacethe column tube from the second end structure, and move the first endstructure's piston through the column tube to its exposed position.Preferably the same drive performs both functions. Preferably the driveis mounted on or adjacent the second end structure.

For the piston to be moved right through the column, it needs to besupported from behind by a structure that can fit into the column tubebehind it, essentially over the full length of the tube. This insertablepiston support structure desirably connects the piston to an operatingdrive, preferably a powered drive such as a hydraulic drive, throughoutits stroke including the position exposed at—and preferably projectingfrom—the second end, so that it can be driven controllably to and fromthe exposed position.

We talk here about pushing the piston through the tube; it should beunderstood that except where the context specifies otherwise this is arelative matter and may involve absolute movement of the tube while thepiston remains fixed, or movements of both elements over differentdistances. The preferred combination of movements will depend to someextent on the dimensions of the components, the operating strokeavailable for the drive(s) used, and on whether (as preferred) the samedrive(s) is/are used for the operations exposing the end structures asis/are used for adjusting the position of the mentioned piston when thecolumn is closed for operation.

In apparatus terms, chromatography apparatus embodying the invention hasa column tube, first and second end structures as described above, andmeans for driving relative movement between the column tube and endstructures from a closed position, in which the first end structure'spiston is fitted inside the tube and the second end structure closes thesecond end of the tube, and an open (maintenance) position in which thesecond end of the column tube is held spaced away from the second endstructure, and the piston of the first end structure is exposed at thesecond end of the tube and preferably projecting beyond it. Preferablythe drive arrangement supports the piston axially via a drive supportbehind the piston, i.e. having an insertion structure which extendsalong inside the column tube in the maintenance position. The drivemeans which carries out this function may drive the column tube and/orthe piston relative to the second end structure; the drive source ispreferably fixed on or fixed relative to the second end structure, andpreferably adjacent that structure. Preferably the drive means is fixeddirectly to the second end structure, e.g. a base of the column. Todrive the piston, the drive means may have a piston drive connectorextending axially outside the column from the second end to the firstend, and connecting past the first end with an insertable supportstructure for the piston as mentioned above. Preferably the drive is viaaxially-movable rods extending up beside the column, e.g.hydraulically-driven rods. A radial connecting structure, such as alifting ring or adjuster flange as referred to previously, may form apart of the drive connector which connects these rods to the insertablepiston support structure. The insertable structure itself may be a setof axial rods extending back from the piston, as in previousconstructions, but of a length enabling the piston to emerge at thesecond end of the column tube.

Preferably a common drive operates both the relative movement between apiston and second end structure and the relative movement between thecolumn tube and first end structure. For this purpose, somewhatanalogous to the structure described previously in relation to FIGS. 1to 5, the drive connection may be selectively connectable/disconnectableto the column tube and/or second end structure, so that they can bemoved either together or relative to one another. However there is noneed for connections dedicated to union of the column tube and secondend structure (cf. the tie rods 73 referred to previously) because thismode of movement may not be needed.

By operating the drive from one end, in practice preferably the base ofthe column which may be a base mounted on a stand, we can provide theadvantages of the invention without relying on overhead structures orseparate units. Nevertheless, the skilled person will appreciate thatthe advantageous exposure of the piston at the opposite end of thecolumn tube may be achieved by other means if extra drives orattachments to other structures are tolerated, e.g. to drive the pistondown from a fixed structure above, and/or to lift the column tube up ordown relative to its base e.g. by a similar means, or to support thetube and drive the base downwardly. In general, use of dedicated drivesfor the different functions simplifies the drive connections but makesthe apparatus more bulky, complicated and expensive overall, to theextent that it may be difficult to mount the various drives whileretaining adequate access to the column area.

As in previous proposals, it is preferred to have one or morenon-driving guide structures engaging the relatively axially moveablecolumn components to maintain and support their axial alignment as theyare driven in relative movement. For example, plural slidable guide rodspassing through openings in the components may be used as describedpreviously. Mechanisms are preferably provided for locking relative tothese structures e.g. guide rods in selected positions, so thatcomponents can be held at selected spaced orientations (particularly foraccess) without relying on (or relying solely on) the drive for thispurpose. A skilled person will appreciate that there are other ways ofproviding detents for holding various axial positions of the components,for safety or otherwise.

Safety stops may also be provided for limiting the extent of availableaxial movement between various components to prevent their exceeding thesafe reach of the structure; these also may be embodied in rods ortensile elements with stop abutments engaging between the components inquestion. The guide rods can be used for this. In present embodiments,the guide rods need not connect to the lifting ring.

Typically these proposals are useful with columns whose column tubes areat least 500 mm in internal diameter, or preferably 800 mm or more, or1000 mm or more. The height of the column tube is preferably at least200 mm, more preferably at least 300 or at least 400 mm. It may be usedwith integrally flanged steel columns or with polymer tubes held betweendiscrete flange plates.

Because the usual use of the system is for gaining access to thepermeable elements of the first and second end structures, thedisposition of axially-extending surround and drive structures needs tobe determined in conjunction with the axial clearances achieved by themechanism so that there is room to get these permeable elements in andout.

Preferably the invention is implemented in a column having one or morepacking and/or unpacking valves enabling the column to be filled with oremptied of packing medium as a slurry. These may be combined valves alsoproviding for flow of process liquids, and preferably access the columninterior through the centre of each end structure, bypassing thepermeable structure.

While the particular kind of drive used for moving the tube and endstructures axially relative to one another is not particularly limited,and indeed these movements may be done manually if necessary, it ispreferred to use a hydraulic drive with plural hydraulic drive unitsdistributed around the column. The skilled person is well aware thatwhere a piston end cell is moved in a column tube, it is important topreserve exactly the axial alignment of the piston in the tube. This isnot straightforward where it is wide, heavy, subject to large forces andsupported at more than one point. In this respect, we propose to detectthe axial positions of plural circumferential drive components (actingon the piston), input the detected positions to a control processor, anduse the control processor to compare the detected positions with oneanother and/or with a predetermined value. The control processor isprogrammed then to control and adjust the rates and/or pressures ofsupply of hydraulic fluid to the respective hydraulic drive units tokeep the piston axially aligned as it moves. This proposal is new anduseful in any chromatography column using multiple hydraulic drives forthe end cell piston; it is itself a separate aspect of our proposals andnot limited to the particular mechanisms described above as aspects ofthe invention.

Returning however to the maintenance proposals, it is preferred that inthe maintenance position the first end structure's piston actuallyprojects from the column tube's second end, and more preferablysufficiently far to expose a peripheral outwardly-directed seal of thepiston. When retracting the piston towards the operational condition,this seal structure rides over the edge of the column tube and might beliable to damage. It may therefore be desirable to adapt the sealstructure and/or column tube conformation at this point to avoid suchdamage. The top opening of a column tube conventionally has a guidechamfer for this purpose, but this is usually undesirable at the bottomend because uniformity at this region is critical for chromatography.Therefore it is preferred to adapt the seal structure, such as byproviding a projecting annular support e.g. of engineering plastics,closely axially adjacent a sealing ring to protect it against possiblydamaging deformations as it retracts into the tube.

Examples of these new proposals are now discussed with reference to theremainder of the following drawings in which:

FIG. 6 is an axial section through a chromatography column, at VI ofFIG. 8;

FIG. 7 is an axial cross-section of the same column at VII of FIG. 8;

FIG. 8 is a top view of the column;

FIG. 9 is an enlarged underneath view (in which, as in FIG. 7, the standhas been omitted for clarity);

FIGS. 10, 11 and 12 are first, second and third stages of an end cellaccess or maintenance procedure involving mesh removal, analogous toFIGS. 1 to 5 above;

FIG. 13 has enlarged detail at XIII of FIG. 7, where a drive rod meetsthe upper tube flange;

FIG. 14 shows detail at XIV of FIG. 7, where the drive rod passesthrough the base plate;

FIG. 15 is enlarged detail at XV of FIG. 7, where a guide rod securesinto the tube flange;

FIG. 16 is enlarged detail at XVI of FIG. 7, where the guide rod passesthrough the base plate, also showing a safety mechanism;

FIG. 17 shows enlarged the bottom of the guide rod, at XVII in FIG. 7;

FIG. 18 is detail at XVIII of FIG. 6, showing securement of the fixedcell plate to the fixed cell backing plate;

FIG. 19 shows enlarged detail of a retaining screw for an end mesh;

FIG. 20 shows enlarged a bed support seal structure, seen also in FIG.14, and FIG. 21 shows enlarged an arrangement for flushing out the sealsof the piston cell.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The column components are broadly similar to those in FIGS. 1 to 5discussed previously. Thus, the cylindrical stainless steel column tube101 has upper and lower integral flanges 111, 112, and the base 105consists of a steel backing plate 152 and a contoured cell plate 153which carries the bed support mesh. Releasable threaded studs 157 holdthe bottom column flange 112 down onto the base, clamping a fixed seal159 described later. The column base 105 stands on support legs 151,here a wheeled mobile support, providing a component space beneath thebase.

Continuing with reference to FIGS. 6 to 9, three hydraulic drivecylinders 108 are mounted to the underside of the base plate 152, andeach operates a drive rod 181 extending up slidably through an openingin the base 105, a corresponding opening in the lower tube flange 112and up to the upper flange 111. The upper flange 111 has correspondingholes, and a drive extension rod 183 has its bottom end passing throughthis flange opening and threadedly secured to the top of the main driverod 181. At the upper flange 111, a pair of releasable nuts 184 can beused to lock the drive rod extension 183 to the flange 111, or releasedso that the rod can slide through it.

The top of each of the three drive rod extensions 183 is bolted into theouter periphery of a lifting ring 107. From its inner periphery, acircumferential series of nine spacer rods 166 depends vertically, theirbottom ends being screwed fixedly into the back plate 162 of the uppercell piston 106. The spacer rods 166 are slightly longer than theinterior axial length of the column tube 101.

Guide rods 171 are provided to guide and limit the movement between thecolumn tube 101 and the base 105 when these are disconnected. The topend of each guide rod 171 is fixed into the top column flange 111,unlike the previously-described system in which they had to extend up tothe lifting ring 7. The bottom of each guide rod passes down throughslide openings in the bottom tube flange 111 and base 5 into a housingsleeve 178 extending down beneath the base 105. The bottom of each guiderod 171 has a projecting stop portion 177 (see also FIG. 17) which, byabutting beneath the plate 105, limits the height to which the tube 101can be lifted above the base.

FIGS. 7 and 16 also show a safety plate 176 which, when the guide rod171 is fully raised, can be slid across to block its return path andthereby support the raised assembly through the guide rods 171.

FIGS. 10, 11 and 12 show the stages involved in gaining access to theend cells of the column. Firstly (FIG. 10) the piston 106 is lowered bythe drives 108 to its lowest available operating position in the tube101. For this, the drive rod extensions 183 must be free to slidethrough the top tube flange 111. The fastener studs 157 are removed torelease the tube 101 from the base 5.

The nuts 184 are then secured to lock the column tube 101 to the drivevia its upper flange 111, and the drive rods 181,183 extended to theirfull height. This height is limited by the abutment of the guide rodstops 177 against the underside of the base plate. The safety slides 176are then pushed across, relieving the drive mechanism of the load. Inthis position, as in previous techniques, the bottom end cell isavailable for access.

To access the upper end cell, however, it is not necessary to re-lowerthe tube 101. Rather, the retaining nuts 184 securing the tube flange111 to the drive rods 183 are released. The tube is then supportedsolely by the guide rods 171. The drive is then partially retracted tothe position shown in FIG. 12, in which the entire front plate and endmesh of the piston end cell 6 emerge from the bottom end of the columntube 101. This is possible because the length of the spacing pillars166, and the vertical reach of the drive rod extensions 183 in the otherdirection, is greater than the length of the tube. The end cellconstruction is then readily accessible for operations of the kinddescribed, and its mesh can be removed or installed through the sameclearance as is used for the bottom cell mesh.

Having thus described the essential advantageous operation of thecolumn, some particular features are now described in a little moredetail and with reference to FIGS. 13 to 21.

FIGS. 13, 14 show details of where the hydraulic drive passes throughthe upper and lower tube flanges 111,112 and base plates 152,153, andthe connection of the first drive rod 181 to the drive rod extension183. FIG. 13 also shows that, at the top opening of the column, thecorner between the column bore and the flange top has a chamfer 114 tofacilitate insertion of the sealed piston structure. The seals areelastomeric rings 169 seated in outwardly-directed peripheral grooves ofthe top cell plate 163, which in this embodiment is machined fromengineering plastics. The plate edge is formed with an intermediate land1631 between the two sealing rings 169, and a front land 1632 whichretains the front sealing ring 169 and also mounts the retaining ring1633 of the removable mesh layer 1634. FIG. 14 shows that the bottomedge of the tube bore has no chamfer, because exact cylindricality iscrucial in this area. When the piston seals 169 are pushed out beyondthe tube end for maintenance, the built-up lands 1631,1632 support themagainst possibly damaging deformation, particularly as the piston isretracted after maintenance.

The seal arrangement at the bottom of the column does not slide.Instead, a mesh clamping ring 157 seats in an annular recess of the baseplate 153 (see also FIG. 20), and has an inward shoulder which traps theedge of the lower mesh 1534 down against a ring seal 159. An opposedupward ring seal 159 engages the bottom face of the column tube.

FIG. 19 shows one of an array of fastening screws used to hold the mesh1534 in place against the underlying end cell plate 153. This plate ismachined with a pattern of surface grooves (not shown) for fluid flowbehind the mesh. The fastening screws 1536 connect through into landsbetween these channels. The maintenance access spacing is sufficient torelease or re-fasten these screws.

FIG. 18 shows a separate set of screws 1537 which keep the base plate152 and bottom end cell plate 153 fixed together even when the studs 157are released to release the column tube.

FIG. 21 shows an arrangement for flushing out the top cell sealconstruction, by forcing in pressurised liquid through a duct leading toopenings in the land 1631 between the two sealing rings 169.

Finally, the hydraulic supplies to the three drives 108 are controllableindependently of one another. Electronic monitors (not shown) read theaxial positions of the drives and compare them, by means of a controlprocessor. The control processor (not shown) is operatively connected tothe hydraulic control and adjusts the hydraulic supplies to therespective drives 108 in dependence on the monitored values, equalisingthe axial extensions of the three drive rods 181. The skilled personwill appreciate that this system is also used when the column is closedand preparing for operation, e.g. in adjusting the compression of thebed of chromatography medium. Any suitable hydraulic fluid may be used.Gas may be used instead.

1-9. (canceled)
 10. A chromatography column apparatus comprising: acolumn tube having first and second ends, and first and second discreteend cell structures which are associated with the respective ends of thecolumn tube and positionable to close off the column tube and therebydefine therein a column space for retaining chromatography medium, inuse of the apparatus; at least the first end cell structure comprising apiston portion fitting slidably in the column tube; wherein the firstend cell structure has an insertable support structure which supportsthe piston portion from behind, connects beyond the first end of thecolumn tube to a drive means for controllably moving the column tube andpiston portion axially relative to one another and for separating thesecond end of the column tube and the second end structure to provideaccess spacing between the second end of the column tube and the secondend cell structure, the support structure having sufficient axial reachfor the piston portion to be exposed at the open second end of thecolumn tube while still supported by the insertable support structure.11. The chromatography column apparatus according to claim 10, whereinthe drive means comprises one or more hydraulic cylinders and one ormore respective axially-extending drive rods.
 12. The apparatus of claim10, further comprising a safety plate movable to block movement of thesecond end of the column tube toward the second end cell structure tomaintain the access spacing, before advancing the piston portion of thefirst end cell structure through the column tube to expose it at theopen second end of the tube.
 13. The apparatus of claim 10, furthercomprising movable guide rods having projecting stops limiting theheight to which the second end of the column tube can be separated fromthe second end cell structure.
 14. The apparatus of claim 12, furthercomprising movable guide rods having projecting stops limiting theheight to which the second end of the column tube can be separated fromthe second end cell structure.
 15. The apparatus according to claim 10,comprising a powered drive, mounted on or adjacent the second endstructure, for separating the column tube and the second end cellstructure to provide the access spacing.
 16. The apparatus according toclaim 10, comprising a powered drive for moving the piston portionrelatively forwardly through the column tube to be exposed at the secondend thereof as aforesaid.
 17. The apparatus according to claim 16,comprising a powered drive for separating the column tube and second endcell structure, and for moving the piston portion through the columntube.
 18. The apparatus according to claim 15, wherein the powered drivecomprises a hydraulically actuatable powered drive.
 19. The apparatusaccording to claim 10, wherein the piston portion is supported frombehind by an insertable support structure that reaches in from the firstend of the column tube, with sufficient axial reach for the front of thepiston portion to reach beyond the second end of the column tube. 20.The apparatus according to claim 10, comprising a powered drive foradvancing the piston portion to the exposed position by means of a driveconnection via the insertable support structure.
 21. The apparatusaccording to claim 20, wherein the powered drive comprises pluralhydraulically-actuated drive rods extending axially up the outside ofthe column tube, the drive rods being circumferentially spaced from oneanother, driven by cylinders mounted at or adjacent the second end cellstructure, and connected to the insertable support structure by a radialconnecting structure which crosses radially above the edge of the columntube at the first end thereof.
 22. The apparatus according to claim 10,wherein the insertable support structure has sufficient axial reach forthe front of the piston portion to project beyond the second end of thecolumn tube for said maintenance.
 23. The apparatus according to claim11, comprising cylinders mounted below the second end cell structure fordriving the drive rods.